NM_006379.5:c.1644-180T>C

Variant names:

• chr7-80751516-A-G
• rs3215357
• NM_006379.5:c.1644-180T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006379.5(SEMA3C):​c.1644-180T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 125,988 control chromosomes in the GnomAD database, including 12,880 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.49 (12880 hom., cov: 29)
• Consequence: SEMA3C NM_006379.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.50
• Publications: 0 publications found

Genes affected

SEMA3C (HGNC:10725): (semaphorin 3C) This gene encodes a secreted glycoprotein that belongs to the semaphorin class 3 family of neuronal guidance cues. The encoded protein contains an N-terminal sema domain, integrin and immunoglobulin-like domains, and a C-terminal basic domain. Homodimerization and proteolytic cleavage of the C-terminal propeptide are necessary for the function of the encoded protein. It binds a neuropilin co-receptor before forming a heterotrimeric complex with an associated plexin. An increase in the expression of this gene correlates with an increase in cancer cell invasion and adhesion. Naturally occurring mutations in this gene are associated with Hirschsprung disease. [provided by RefSeq, May 2017]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA3C	NM_006379.5	c.1644-180T>C		intron_variant	Intron 15 of 17	ENST00000265361.8	NP_006370.1
SEMA3C	NM_001350120.2	c.1698-180T>C		intron_variant	Intron 15 of 17		NP_001337049.1
SEMA3C	NM_001350121.2	c.1470-180T>C		intron_variant	Intron 16 of 18		NP_001337050.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA3C	ENST00000265361.8	c.1644-180T>C		intron_variant	Intron 15 of 17	1	NM_006379.5	ENSP00000265361.3
SEMA3C	ENST00000419255.6	c.1644-180T>C		intron_variant	Intron 15 of 17	2		ENSP00000411193.2

Frequencies

GnomAD3 genomes AF: 0.491 AC: 61789 AN: 125928 Hom.: 12882 Cov.: 29

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.528

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.551

Gnomad FIN AF: 0.504

Gnomad MID AF: 0.466

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.497

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.491 AC: 61809 AN: 125988 Hom.: 12880 Cov.: 29 AF XY: 0.486 AC XY: 29865 AN XY: 61392

African (AFR) AF: 0.457 AC: 14961 AN: 32764

American (AMR) AF: 0.449 AC: 5464 AN: 12156

Ashkenazi Jewish (ASJ) AF: 0.528 AC: 1624 AN: 3078

East Asian (EAS) AF: 0.249 AC: 575 AN: 2308

South Asian (SAS) AF: 0.551 AC: 2138 AN: 3880

European-Finnish (FIN) AF: 0.504 AC: 4626 AN: 9174

Middle Eastern (MID) AF: 0.466 AC: 124 AN: 266

European-Non Finnish (NFE) AF: 0.520 AC: 31071 AN: 59788

Other (OTH) AF: 0.491 AC: 863 AN: 1758

Alfa AF: 0.558 Hom.: 29955

Bravo AF: 0.397

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.43
DANN	Benign	0.19
PhyloP100		-2.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3215357; hg19: chr7-80380832; COSMIC: COSV54856980;